PROJECT SUMMARY. Polycystic ovary syndrome (PCOS) is a complex endocrine disorder whose symptoms and co-morbidities have far-reaching implications for the health and well-being of women across the lifespan. While the name of this condition implies a specific abnormality in ovarian morphology, substantial controversy surrounds the relevance of polycystic ovaries (PCO) to the diagnosis and clinical spectrum of PCOS. Evidence of PCO in healthy women has cast doubt upon the specificity of PCO to the condition of PCOS, and its presence in both women with hyperandrogenic (PCOS) and normoandrogenic anovulation (NA-Anov) has challenged its utility to inform progression of the disease and/or response to treatment. In line with these findings, we recently proposed new thresholds to redefine PCO. These new criteria represented a major change in the definition of PCO owing to the improved resolution of new technology. While these criteria are expected to reduce the number of false positive diagnoses in healthy women, they are still limited. They do not account for factors known or suspected to influence ovarian morphology ? nor do they provide any insight into the etiology or degree of disordered folliculogenesis in PCOS. This project aims to refine the sonographic definition of PCO by using state- of-the-art ultrasound imaging technology and standardized approaches to contrast ovarian morphology across a broad spectrum of women with PCOS and NA-Anov. We believe that the basis for defining PCO on ultrasonography should reflect an understanding of antral follicle development in these conditions. The central hypothesis proposed is that ovarian morphology on ultrasonography captures unique disruptions in antral follicle development that can inform both clinical and functional outcomes in women with anovulatory disorders. The goals of this project are to develop criteria for PCO that: 1) maintain specificity for PCOS compared to NA-Anov, 2) account for any confounding effect of adiposity on ovarian morphology, 3) inform on the degree of impaired folliculogenesis and 4) reliably predict the ovulatory response to weight loss. Any utility of surrogate markers of PCO (i.e. anti-Mllerian hormone) to match or exceed the performance of ultrasound will be determined. By providing definitions for PCO that reflect functional outcomes, this research will expand the role of ultrasonography in the clinical evaluation of PCOS and usher new approaches for tailored interventions that account for the spectrum of disordered folliculogenesis across anovulatory conditions. These efforts to clarify the relevance of PCO morphology are consistent with prioritized areas of research identified by the recent NIH Evidence-Based Methodology Workshop on PCOS.